Flashcards in Acute Inflammation Deck (22):
What is acute inflammation?
Inflammation is a response by tissue to limit tissue damage, it is innate, immediate and early, and stereotyped meaning that it is exactly the same each time. It does not last that long from a few minutes to a few days. There is a vascular and cellular reaction of tissue which is an accumulation of fluid exudate and neutrophils in tissues. This in controlled by a variety of chemical mediators derived from plasma or cells. It is protective although it can lead to localised complications.
What can cause acute inflammation?
• Microbial infections e.g. pyogenic organisms - puss forming molecules
• Hypersensitivity reactions
• Physical agents e.g. heat, mechanical forces
• Tissue necrosis
What are the clinical sign of acute inflammation?
The clinical signs of inflammation are: Rubor = redness, Tumor = swelling, Calor = heat and Dolor = pain (and maybe loss of function).
Describe the first changes that occur in acute inflammation?
1. Transient vasoconstriction of arterioles lasting only a few seconds but unknown why
2. Vasodilation of arterioles and then capillaries which increases the blood flow to the injured tissue causing heat and redness
3. Increased Permeability of blood vessels causing an exudation of protein rich fluid into tissues and as a result of this a thickening of the blood and so slowing of circulation leading to the swelling
4. As a consequence of all this you get stasis which is slowing down and stopping of blood flow.
What are the main chemical mediators for acute inflammation?
Histamine offers an early immediate response and is a chemical released form mast cells, basophils and platelets in response to many different stimuli such as physical damage, immunological reactions, C3a and C5a (compliment 3a and 5a), factors from neutrophils and platelets and IL-1 (interleukin 1 – a type of cytokine). Histamine causes vascular dilation, endothelial cell contraction and increased permeability. Whilst there are also persistent response mediators such as leukotrienes, bradykinin, serotonin and prostaglandins which all cause the same effects as histamine.
Describe the 2nd change that occurs in acute inflammation and why it occurs.
This is fluid loss from vessels and goes according Starling’s law. So fluid will move out as an exudate if there is a high hydrostatic pressure and a high colloid osmotic pressure of the interstitium.
The way this occurs in inflammation is:
• Arteriolar dilation leading to increase in hydrostatic pressure
• Increased permeability of the vessel walls leading to loss of protein into interstitium
What is the difference between transudate and exudate?
Transudate is just due to increase hydrostatic pressure and there is no excess movement of protein.
Exudate involves proteins as well and is what you get in inflammation
Describe the mechanisms of vascular leakage
• Endothelial contraction forming gaps mediated by histamine and leukotrienes
• Cytoskeleton reorganisation forming gaps mediated by cytokines IL-1 and TNF
• Direct injury such as toxic burn or chemicals
• Leukocytes dependant injury such as toxic oxygen species and enzymes from leukocytes
• Increased transcytosis – normal movement of ions across channels in the endothelial cytoplasm mediated by VEGF (vascular endothelial growth factor)
What is the importance of fibrin in the exudate formation?
Fibrin is a very important inflammatory response as the exudate is fibrin rich and becomes activated making an effective haemostatic plug and making things sticky to keep them together. Fibrin therefore localises all the responses in inflammation.
What are the 4 different types of exudate
1. Pus/Abscesses – this is a white fluid filled with neutrophils
2. Haemorrhagic – red appearance as it contains a lot of red blood cells and usually indicates significant vascular damage
3. Serous Exudate – contains plasma proteins but few neutrophils suggesting no infection, they are usually clear and differ from transudate because they don’t contain fibrinogen
4. Fibrinous Exudate – contains a large amount of fibrin
What are the main cells involved in acute inflammation?
Neutrophil leukocytes/polymorphs are the main cells of inflammation. These cells accumulate around the edges of blood vessels and emigrate into the swollen tissues when inflammation is taking place.
What are the 4 stages of neutrophil emigration
1. Margination – stasis causes neutrophils to line up at the edge of the blood vessels
2. Rolling – the cells then roll along the endothelium getting slightly stuck
3. Adhesion – they stick more avidly
4. Emigration – the cells move through into the tissue fluid
What is diapedesis?
Neutrophils get through the wall by changing shape and relaxation of the inter-endothelial cell junctions. The basement membrane is digested and rebuilt after the cell passes through. This process is called diapedesis and the neutrophils move by chemotaxis.
What facilitates phagocytosis by neutrophils?
This is facilitated by opsonins mainly C3
What are the two mechanisms of cell death after it has been engulfed?
• O2 dependant involves the respiratory burst from the formation of superoxide and hydrogen peroxide
• O2 Independent involves lysozyme and hydrolases, Bacterial permeability increasing protein (BPI and cationic proteins (defensins)
How does fluid exudation combat injury?
This delivers plasma proteins to the area of injury such as immunoglobulins, inflammatory mediators and fibrinogen. It also dilutes toxins and increases lymphatic drainage which delivers micro-organisms to phagocytes and antigens to the immune system.
What general complications can occur due to acute inflammation?
This usually involves the blocking of some kind of cavity or tube resulting in a build-up of bacteria that causes more inflammation and maybe infection and may prevent the function of this part of the body. Also the exudate can get into places you don’t want it such as pericardial sac causing cardiac tamponade. May also cause too much of a loss of fluid if it’s a burn and finally the pain and loss of functions may become difficult if it lasts a long time.
What systemic affect are there of acute inflammation?
• Fever – due to endogenous pyrogens such as IL-1 and TNF alpha this is usually treated with aspirin which reduces this fever
• Leucocytosis – formation of new neutrophils which is very useful in clinical practice to see if they have an infection of some kind
• Acute phase response – change in the plasma levels of proteins leading to Decreased appetite, raised pulse rate, altered sleep patterns and changes in plasma concentrations of acute phase proteins
• If inflammation doesn’t work then you can get systemic acute inflammation leading to shock which is circulatory failure
What are the 4 possible outcomes of acute inflammation?
1. Complete resolution – most common: changes gradually reverse and vascular changes stop, exudate fluid drains through lymphatics and neutrophils die and break up and are carried away and fibrin is broken down – if tissue architecture is completely destroyed complete resolution is not possible. Resolution can happen as all mediators have a short half-life or they may be inactivated or diluted
2. Continued acute inflammation – abscess. The fluid exudate forces tissue apart, liquefactive necrosis in the centre which causes high pressure and squash adjacent structure causing pain
3. Goes onto form chronic inflammation
What is hereditary angio-oedema?
Hereditary angio-oedema (oedema in the airways) – deficiency in C1 inhibitor esterase (breaks down C1) , C1 cleaves C2 and C4 into C3 and also inhibits Bradykinin uninhibited Bradykinin greatly increases the permeability of endothelial cells
What is alpha 1 antitrypsin deficiency?
Alpha-1 antitrypsin deficiency – this normally inhibits elastase which breaks down lung and liver tissue so the deficiency causes lung disease and liver cirrhosis